With the construction of the largest dam in Africa, the Grand Ethiopian Renaissance Dam (GERD) along the Blue Nile, the Nile is back in the news. This, combined with Bujagali Dam on the White Nile are expected to bring ramification to the downstream countries. A comprehensive analysis of the Nile's waters (surface, soil moisture and groundwater) is, therefore, essential to inform its management. Owing to its shear size, however, obtaining in-situ data from “boots on the ground” is practically impossible, paving way to the use of satellite remotely sensed and models' products. The present study employs multi-mission satellites and surface models' products to provide, for the first time, a comprehensive analysis of the changes in Nile's stored waters' compartments; surface, soil moisture and groundwater, and their association to climate variability (El Niño Southern Oscillation (ENSO) and Indian Ocean Dipole (IOD)) over the period 1992–2016. In this regard, remotely sensed altimetry data from TOPEX/Poseidon (T/P), Jason-1, and Jason-2 satellites along with the Gravity Recovery And Climate Experiment (GRACE) mission, and the Tropical Rainfall Measuring Mission Project (TRMM) rainfall products are applied to analyze the compartmental changes over the Nile River Basin (NRB). This is achieved through the creation of 62 virtual gauge stations distributed throughout the Nile River that generate water levels, which are used to compute surface water storage changes. Using GRACE total water storage (TWS), soil moisture data from multi-models based on the Triple Collocation Analysis (TCA) method, and altimetry derived surface water storage, Nile basin's groundwater variations are estimated. The impacts of climate variability on the compartmental changes are examined using TRMM precipitation and large-scale ocean-atmosphere ENSO and IOD indices. The results indicate a strong correlation between the river level variations and precipitation changes in the central part of the basin (0.77 on average) in comparison to the northern (0.64 on average) and southern parts (0.72 on average). Larger water storages and rainfall variations are observed in the Upper Nile in contrast to the Lower Nile. A negative groundwater trend is also found over the Lower Nile, which could be attributed to a significantly lower amount of rainfall in the last decade and extensive irrigation over the region.